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JSB Paper-of-the-Year award 2013 to Laure Yatime et al.

The paper "Structural insights into the high affinity binding of cardiotonic steroids to the Na+,K+-ATPase"
by Laure Yatime, and Mette Laursen among others, has been awarded the "Paper-of-the-Year" award 2013 by Journal of Structural Biology.

General overview of the Na+,K+-ATPase E2P:ouabain complex. (C) Cartoon representation of the E2P:ouabain complex determined at 4.6 Å resolution. The ouabain molecule is displayed as a sphere representation in green and red within the TM segment.

Abstract

The Na+,K+-ATPase belongs to the P-ATPase family, whose characteristic property is the formation of a phosphorylated intermediate. The enzyme is also a defined target for cardiotonic steroids which inhibit its functional activity and initiate intracellular signaling. Here we describe the 4.6 Å resolution crystal structure of the pig kidney Na+,K+-ATPase in its phosphorylated form stabilized by high affinity binding of the cardiotonic steroid ouabain. The steroid binds to a site formed at transmembrane segments ?M1-?M6, plugging the ion pathway from the extracellular side. This structure differs from the previously reported low affinity complex with potassium. Most importantly, the A domain has rotated in response to phosphorylation and ?M1-2 move towards the ouabain molecule, providing for high affinity interactions and closing the ion pathway from the extracellular side. The observed re-arrangements of the Na+,K+-ATPase stabilized by cardiotonic steroids may affect protein-protein interactions within the intracellular signal transduction networks.